反应详情

3-[6-(Azetidine-1-carbonyl)pyridin-3-yl]oxy-5-hydroxy-N-(5-methylpyrazin-2-yl)benzamide (Intermediate 1) (203 mg, 0.5 mmol), 3-hydroxyoxolan-2-one (CAS no. 19444-84-9) (0.078 mL, 1 mmol) and triphenyl phosphine (262 mg, 1 mmol) in anhydrous THF (10 mL) under argon at 0° C. was treated dropwise with DIAD (0.20 mL, 1 mmol). The mixture allowed to warm to room temperature and stirred for 16 hours. The solvent was removed by evaporation under reduced pressure and the residue was purified by chromatography on silica eluting with 0-4% methanol:DCM to give product (212 mg 86%). 1H NMR δ (400 MHz, CDCl3) 2.29 (quintet, 2H), 2.40-2.48 (m, 1H), 2.50 (s, 3H), 2.69-2.78 (m, 1H), 4.18 (t, 2H), 4.33 (q, 1H), 4.49 (t, 1H), 4.64 (t, 2H), 4.99 (t, 1H), 6.89 (s, 1H), 7.18 (s, 1H), 7.33 (d, 1H), 7.36 (s, 1H), 8.06 (d, 1H), 8.08 (s, 1H), 8.28 (s, 1H), 8.41 (s, 1H), 9.46 (s, 1H); m/z 490 (M+H)+.

1. customThe solvent was removed by evaporation under reduced pressure
2. customthe residue was purified by chromatography on silica eluting with 0-4% methanol
3. customDCM to give product (212 mg 86%)